The present invention relates to a method and apparatus for measuring vagal tone, a neurophysiological signal generated within the brain and transmitted to the heart for controlling heart rate. The present invention also relates to a method of and apparatus for diagnosing medical conditions and, particularly but not exclusively, autonomic dysfunction conditions such as is found in spongiform encephalopathies.
The two neural mechanisms for controlling heart rate in the human and animal are the sympathetic and parasympathetic nervous systems. Sympathetic activity gives rise to relatively slowly varying changes in heart rate (e.g. below 0.1 Hz). Parasympathetic activity is generated in a region of the brain known as the Vital Centre, which is located in the lower medulla, and is transmitted to receptors in the sino-atrial node of the heart along the vagus nerve. The vagus nerve is myelinated such that parasympathetic activity is conveyed rapidly to the heart. The continuous flow of signal conveyed along the vagus nerve is termed the xe2x80x98vagal tonexe2x80x99.
Vagal tone tends to act as a xe2x80x98brakexe2x80x99 on the heart, slowing the heart rate to a lesser or greater extent. A high level of vagal tone also tends to give rise to relatively large and rapid fluctuations in heart rate period. Conventionally, it is these fluctuations which are used to measure vagal tone from recorded electrocardiograms (ECG) and to xe2x80x98isolatexe2x80x99 vagal tone from the relatively slowly varying effects of sympathetic activity. More particularly, vagal tone is generally measured by considering an ECG over a relatively long time period (e.g. 1000 beats) and evaluating the mean of the differences between consecutive beats (see for example Heart Rate variability, Eds. Merek Malik and A. John Comm. 1995, Futura Publishing).
It is believed that certain diseases and conditions (e.g. diabetes and respiratory tract obstructions) can adversely effect cardiac function via parasympathetic activity. There has long been a desire therefor a method for accurately measuring vagal tone for the purpose of monitoring, and possibly diagnosing, such diseases and conditions, a desire which is not fully satisfied by conventional methods of measuring vagal tone. An accurate measure of vagal tone could also be useful in monitoring the activity of pharmaceuticals which are intended to effect parasympathetic activity or which have this effect as a side effect.
The present invention has resulted from the realization that heart rate variability results in the frequency modulation of what is effectively a constant frequency nominal heart rate. This is analogous to frequency modulation of, for example, radio signals where an underlying carrier signal of constant frequency has its instantaneous frequency modulated by an information or modulating signal.
One known apparatus for providing a measure of vagal tone or other physiological signals in a human or animal patient is disclosed in International Patent Application No. WO-A-96/08992 (Ramot University Authority for Applied Research and Industrial Development Ltd). This document describes an apparatus comprising an input means for receiving an ECG signal from a patient, a detection means coupled to the input means for detecting QRS waveforms in the ECG signal and for generating timing signals corresponding to the periods between consecutive QRS waveforms, and frequency demodulation means for demodulating the timing signals in order to produce a signal which may be used to provide a measure of vagal tone. However, this apparatus is extremely complicated, and so difficult to use effectively. There is a need for a less complicated system.
It is an object of the present invention to provide an apparatus and method for measuring vagal tone in real time from ECG recordings taken from a human or animal patient which obviates or mitigates at least one disadvantage of existing apparatus and methods.
According to a first aspect of the present invention there is provided apparatus for providing a measure of vagal tone in real time in a human or animal patient and comprising:
a) input means for receiving an ECG signal obtained from a patient;
b) detection means coupled to said input for detecting QRS waveforms in said ECG signal and for generating timing signals indicative of the periods between consecutively received QRS waveforms; and
c) frequency demodulation means coupled to said detection means for demodulating said timing data substantially in real time and for generating a signal corresponding to a frequency modulation signal in said ECG signal, wherein said generated signal is used to provide said measure of vagal tone;
the demodulation means comprising an integrator coupled to the detection means for receiving said fixed length pulses and a high pass filter and a low pass filter coupled separately to the integrator for receiving the output of the integrator, the output of the high pass filter being coupled to a first voltage controlled oscillator via a second integrator and the output of the low pass filter being coupled to a second voltage controlled oscillator, the outputs of the two voltage controlled oscillators being coupled to respective inputs of a phase comparator arranged to generate at its output a signal indicative of the phase difference between the two input signals.
The present invention has resulted from the realisation that heart rate variability results in the frequency modulation of what is effectively a constant frequency nominal heart rate. This is analogous to frequency modulation of for example radio signals where an underlying carrier signal of constant frequency has its instantaneous frequency modulated by an information or modulating signal.
Preferably, the detection means is arranged to compare received portions of the ECG signal against a stored expected QRS waveform (or portion thereof), to identify when a QRS complex is received. Preferably, said timing signal comprises a sequence of fixed length pulses which are generated upon receipt of a QRS waveform. The spacing between the pulses of the sequence therefore corresponds to the spacing between the received QRS waveforms.
The frequency demodulation means of the present invention may be a simple frequency discriminator, for example comprising a differentiator in series with an envelope detector. Alternatively, the frequency demodulation means may comprise a phase locked loop (PLL) incorporating a voltage controlled oscillator (VCO) substantially tuned to the nominal constant heart rate. This nominal rate or frequency of the VCO may be preset or may be determined by sweeping the VCO frequency across a suitable range until a lock is obtained with the nominal heart rate frequency of the received ECG signal. A possible problem with these types of FM demodulators however is that they may not function adequately where large variations of the nominal heart rate occur. For example, it is possible for the nominal heart rate in a human to vary between 30 and 200 beats per minute (bpm), with the vagal tone causing high frequency modulation of the nominal rate.
The component parts of the FM demodulator are selected so that for a constant, or slowly varying nominal heart rate, the outputs of the two voltage controlled oscillators are substantially in phase. In particular, the first mentioned integrator may have a time constant of between 1.0 and 2.5 seconds, e.g. 2 seconds. Preferably, the second mentioned integrator also has a time constant selected from this range.
The output from the phase comparator is preferably coupled to a third integrator, which again may have a time constant selected from the range 1.0 to 2.5 seconds.
Preferably, a pre-set DC bias is added to the output of the third integrator to ensure that the resulting summed signal always exceeds zero.
Preferably, the apparatus of the present invention comprises a filter coupled to the frequency demodulation means (or incorporated into that means) for filtering the frequency modulating signal to remove noise and other unwanted signal components. In particular, the filters may be arranged to remove signal components which arise from sympathetic control of the heart rate. As discussed above, sympathetic activity gives rise to relatively low frequency variations in heart rate and the filter may therefore comprise a low pass and/or high pass filter for allowing removal of low frequency sympathetic components of the modulation signal.
The apparatus preferably comprises signal processing means for converting the generated signal into a linear vagal scale (LVS).
The apparatus of the present invention may be implemented in hardware or in software. Alternatively, the apparatus may be implemented by way of combination of hardware and software components.
In one embodiment, the apparatus is provided as a hand-held unit which has a display for displaying measured vagal tone.
According to a second aspect of the present invention there is provided apparatus for measuring vagal tone from an ECG according to the above first aspect of the present invention in combination with means for recording the ECG, coupled to said input.
The recording means may comprise for example electrodes for attachment to the patient and amplifiers for pre-amplifying the recorded ECG.
According to third aspect of the present invention there is provided a method for providing a measure of vagal tone from an ECG recorded from a human or animal patient, the method comprising the steps of:
detecting the occurrence of QRS waveforms in the ECG signal;
generating timing signals indicative of the time period between consecutively received QRS waveforms;
frequency demodulating said timing signal in real time to obtain a frequency modulation signal, wherein said modulation signal is used to provide said measure of vagal tone;
filtering the ECG, the timing signal, or the modulation signal to remove low frequency components (e-g. due to sympathetic activity);
the frequency demodulating step comprising integrating the generated pulse sequence, and separately high pass and low pass filtering the integrated signal, the high pass filtered signal then being integrated and the resulting signal used to frequency modulate a carrier signal, the low pass filtered signal being separately used to frequency modulate a further carrier signal and the phase differences between the two modulated carrier signals determined.
For a better understanding of the present invention and in order to show how the same may be carried into effect reference will now be made, by way of example, to the accompanying drawings in which: